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Nicola, Marina Lazzari. "Efeitos do tabagismo sobre o transporte mucociliar nasal, propriedades físicas do muco, pH do condensado do ar exalado, celularidade e citocinas de lavado nasal de jovens." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5170/tde-29042014-104441/.
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O tabagismo está fortemente associado ao desenvolvimento da Doença Pulmonar Obstrutiva Crônica, porém poucos estudos que relatam alterações funcionais ou inflamatórias nas vias aéreas superiores em jovens são encontrados na literatura. Nosso objetivo foi investigar as alterações funcionais e inflamatórias nas vias aéreas superiores e inferiores em jovens tabagistas com idade igual ou inferior a 35 anos. Setenta e dois indivíduos participaram do estudo: 32 jovens não tabagistas (JNT) saudáveis (21±4 anos, 29 homens) e 40 jovens tabagistas subdivididos de acordo com a carga tabágica: menor que 2,5 anos-maço (< 2,5) (19±2 anos, 20 homens) e igual ou maior que 2,5 anos-maço (>= 2,5) (24 ± 5 anos, 17 homens e três mulheres). Foram avaliados os dados demográficos, os dados clínicos, os sintomas de desconforto das vias aéreas por meio do questionário SNOT-20, os volumes e capacidades pulmonares por meio do teste de função pulmonar, o transporte mucociliar nasal por meio do teste de tempo de trânsito da sacarina, a propriedade de superfície do muco nasal por meio do ângulo de contato, a inflamação na cavidade nasal por meio da contagem total e diferencial das células e citocinas em lavado nasal e a inflamação de vias aéreas inferiores por meio do pH do condensado do ar exalado. Observamos neste estudo que os jovens tabagistas >= 2,5 foram mais velhos comparados aos JNT e com os tabagistas < 2,5 (p < 0,01). Comparados com os JNT, os tabagistas >= 2,5 apresentaram maior índice de massa corporal (p=0,036), de frequência cardíaca (p=0,001) e de pressão arterial sistólica (p=0,036). Os tabagistas >= 2,5 apresentaram maior queixa sobre tosse (p=0,05) e secreção nasal escorrendo para a garganta (p=0,016) quando comparados com os JNT e tabagistas < 2,5. Não encontramos diferenças significativas na pontuação total do questionário SNOT-20 (p=0,140), nos valores do teste de função pulmonar e nos valores do ângulo de contato (p=0,803) entre os grupos. O tempo de trânsito da sacarina foi significativamente menor nos jovens tabagistas (5,9 ± 3,1 minutos) quando comparados aos JNT (7,7 ± 4,1 minutos, p=0,033). Na análise do lavado nasal encontramos maior número de células totais em tabagistas < 2,5 (48+-14) e tabagistas >= 2,5 (37+-25) comparados aos JNT (24+-12, p < 0,001). Encontramos também maior número de macrófagos (p=0,001), células ciliadas (p=0,008) e células caliciformes (p=0,004) nos tabagistas < 2,5 e tabagistas >= 2,5 quando comparados aos JNT, e maiores concentrações de mieloperoxidase nos tabagistas < 2,5 comparados aos tabagistas >= 2,5 (p=0,005). Os valores do pH do EBC foram menores em tabagistas >= 2,5 (7,65 ± 0,42) comparados com os tabagistas < 2,5 (7,83 ± 0,26) e com os JNT (7,90 ± 0,21, p=0,038). Por meio de análise de regressão linear, verificamos um efeito dose-dependente significativo do tabagismo sobre a redução dos valores do pH do EBC (r=-0,47, p < 0,001). Concluímos que o tabagismo em jovens tabagistas com idade igual ou inferior a 35 anos induz alterações do transporte mucociliar nasal, inflamação nasal e inflamação em vias aéreas inferiores e que essas alterações estão associadas à carga tabágica<br>Cigarette smoking is strongly associated with the development of Chronic Obstructive Pulmonary Disease, but few studies that reported functional or inflammatory changes in upper airway in young are found in the literature. We aimed to evaluate the effects of smoking on nasal mucociliary clearance, the mucus surface property and if there is inflammation in the nasal cavity and lower airways in young smokers aged less than 35 years. Of the 200 individuals contacted by telephone, 72 individuals entered in the study: 32 healthy young nonsmokers (YNS) (21 ± 4 years, 29 male) and 40 young smokers, subdivided according to smoking history: less than 2.5 pack-years (< 2.5) (19 ± 2 years, 20 male) and 2.5 pack-years or more ( >= 2.5) (24 ± 5 years, 17 male and three female). We assessed demographic data, clinical data, SNOT-20 questionnaire for symptoms of airway discomfort, the volumes and lung capacities by the pulmonary function test, the nasal mucociliary clearance using the saccharine transit test, the mucus surface property by the contact angle, the inflammation in the nasal cavity by the total and differential count of cells and cytokines in nasal lavage and inflammation of the lower airways by the exhaled breath condensate pH. In this study, we observed that young smokers >= 2.5 were older compared to YNS and smokers < 2.5 (p < 0.01). Compared with YNS, smokers >= 2.5 had higher body mass index (p=0.036), heart rate (p=0.001) and systolic blood pressure (p=.036). Smokers >= 2.5 complained more about cough (p = 0.05) and post-nasal discharge (p=0.016) when compared to YNS and smokers < 2.5. No significant differences were found in the total score of the SNOT-20 (p=0.140), in the pulmonary function test and mucus contact angle (p=0.803) between groups. The saccharine transit time was significantly lower in young smokers (5.9 ± 3.1 minutes) compared to YNS (7.7 ± 4.1 minutes, p=0.033). The number of total cells in nasal lavage fluid were greater in smokers < 2.5 (48±14) and smokers >= 2.5 (37 ± 25) compared to YNS (24 ± 12, p < 0.001). We also found greater number of macrophages (p=0.001), ciliated cells (p=0.008) and goblet cells (p = 0.004) in smokers < 2.5 and smokers >= 2.5 compared to YNS and a higher concentration of myeloperoxidase in smokers < 2.5 compared to smokers >= 2.5 (p=0.005). The EBC pH were lower in smokers >= 2.5 (7.65 ± 0.42) compared with smokers < 2.5 (7.83 ± 0.26) and with YNS (7.90 ± 0.21, p=0.038). Linear regression analysis confirmed a significant dose-dependent effect of smoking in decreasing EBC pH (r= -0.47, p < 0.001). We conclude that cigarette smoking induces changes in nasal mucociliary clearance, nasal inflammation and inflammation in the lower airways in young smokers aged less than 35 years and these changes are associated with smoking history
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Hulterström, Anna Karin. "Silicone obturators and the bacterial flora in symptomatic nasal septal perforations." Doctoral thesis, Umeå universitet, Tandteknikerprogrammet, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-60831.
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Background A perforation in the nasal septum can cause symptoms such as bleeding, obstruction, crusts and pain, and can be a challenge to treat. Surgery is the treatment of choice, but disease, size of the perforation, or the patient’s wish may contradict surgery. A custom-made silicone obturator is a successful treatment option, but little is known how this treatment affects the microbial flora. The purposes of this thesis were (i) to investigate the microbial flora around symptomatic nasal septal perforations before treatment, (ii) during and after a 12-month treatment period with a custom-made obturator, (iii) to compare the microbial flora around symptomatic perforations with the flora from the same area of the septum in healthy individuals, (iv) to investigate the microbial colonization of the silicone obturator, and (v) also to investigate the water sorption, solubility and if the wettability of silicones are affected by water. The hypotheses were (i) that the bacterial flora around symptomatic perforations would not differ from that found in healthy individuals, apart from a possible presence of Helicobacter pylori; (ii) the bacterial flora would change in composition during the course of treatment and that microorganisms and proteins could be seen on the surface of the silicone obturators; (iii) a material that has adsorbed water would also show an increase in wettability and the surface free energy of the material. Methods Twenty-seven patients and 101 healthy individuals volunteered. Swabs were made around the rim of the perforation, or on the septum in the locus Kisselbachi area in the healthy individuals. Bacteria and fungi were isolated and identified with standard laboratory techniques. A biopsy of the granulated tissue at the perforation was taken and cultivated for Helicobacter pylori. Swabs were also taken three, six and twelve months after inserting the obturator. The obturator was analysed after being used twelve months in the nose. Seven silicones were tested for water sorption and solubility according to ISO standards 1567:1999 and ISO 10477:2004. The change in wettability was examined by measuring the contact angle with a contact goniometer at various stages of the sorption/solubility test. Results Staphylococcus aureus was present in 88% of the untreated patients. With treatment a significant reduction of S. aureus occurred to 54.5% (p<0.05). In the healthy group S. aureus was present in 13% of the subjects. No Helicobacter pylori could be cultivated from the biopsies taken of the granulated tissue at the perforation. The flora round the untreated perforation was dominated by S. aureus with few other bacterial species detected. In the healthy group there was a diversified flora with both aerobic and anaerobic bacteria. SEM revealed a rough surface on the silicone obturator and crazing of the silicone surrounding the pigment granules. Both bacteria and proteins could be seen on the obturators in SEM. Candida albicans was detected in one obturator, but not in the mucosal swab at the corresponding time. That patient had, however, been treated for Candida in the nose six months prior to the last visit in the study. Wettability was affected but did not increase with amount of adsorbed water. Some materials showed an increase and some a decrease in the surface-free energy. The tested addition silicones showed little sorption and solubility. Conclusions The patients with symptomatic perforations of the nasal septum had a bacterial flora totally dominated by S. aureus. The massive presence of S. aureus around symptomatic perforations may have an impact on the persistence of the granulated and inflamed tissue present in symptomatic perforations, thus forming a vicious circle with bleeding and crustation. S. aureus dominance in the mucosa surrounding symptomatic perforations was diminished by using a custom-made obturator. The microbial flora became more diversified with the treatment, although not resembling the flora in healthy individuals. The microbial flora of the obturators was similar, but not the same as the corresponding mucosal flora. The discovery of Candida in the obturator of a patient who had been treated for Candida in the nose six months earlier suggests that obturators need to be exchanged when fungal infections are being treated to prevent the fungus from re-infecting the patient at a later stage. The silicone had a rough surface and a poor wettability, both aspects favours colonization of microorganisms. The silicone was negatively affected by the colouring pigments, this should be considered when colouring is not necessary. The slight, but existing solubility of silicones emphasises the importance of using medical grade silicones that are more purified than industrial silicones.
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Grudemo, Hans. "Rhinostereometry and laser doppler flowmetry : simultaneous measurements of inflammation and steroid effects in normal and allergic human nasal mucosa /." Stockholm, 2000. http://diss.kib.ki.se/2000/20000310grud/.
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Franchini, Michelle Lisidati. "Efeitos do oxigênio umidificado e não umidificado via cateter nasal sobre o transporte mucociliar e muco nasal." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5170/tde-20052016-154206/.
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O transporte mucociliar (TMC) é um mecanismo básico de defesa do sistema respiratório necessário na resistência à infecção. A efetividade desse mecanismo de defesa depende da composição e profundidade do muco, da integridade e da função dos cílios e da interação muco-cílio. O objetivo deste estudo foi investigar os efeitos crônicos do oxigenoterapia de baixo fluxo via cateter nasal com e sem umidificação sobre o TMC nasal, nas propriedades físicas do muco, na inflamação e nos sintomas de vias aéreas em pacientes com hipoxemia crônica com necessidade de oxigenoterapia domiciliar de longo prazo (>15 horas/dia). Dezoito pacientes (idade média de 68 anos, 7 do sexo masculino, índice de massa corpórea (IMC) médio de 26 kg/m2, 66% com doença pulmonar obstrutiva crônica (DPOC), 60% com hipertensão arterial (HAS) e ex-tabagistas) iniciando oxigenoterapia de baixo fluxo via cateter nasal foram randomizados para o grupo Oxigênio Seco (n=10) ou Oxigênio Umidificado (n=9). Os pacientes foram avaliados nos tempos: basal, 12 horas, 7 dias, 30 dias, 12 meses e 24 meses para o TMC nasal por meio do teste de trânsito da sacarina, as propriedades físicas do muco por meio de ângulo de contato, a inflamação por meio de quantificação do número total de células e diferenciais e da concentração de citocinas no lavado nasal assim como para sintomas por meio do questionário SNOT-20. O sintoma mais importante relatado por pacientes no basal foi tosse que melhorou após 7 dias de oxigenoterapia. No nosso estudo, os pacientes de ambos grupos apresentaram prolongamento significativo (40%) do TMC nasal ao longo do estudo. O lavado nasal mostrou um aumento das proporções de neutrófilos, das células caliciformes e da concentração do fator de crescimento epidermal (EGF) assim como reduções em macrófagos e concentrações de interferon alfa (IFN-alfa), interleucina (IL)-8 e IL-10 ao longo do estudo. Não houve alterações na proporção de células ciliadas, na concentração de IL-6 e no ângulo de contato do muco em ambos os grupos. A tosse e os sintomas de sono diminuiram significativamente em ambos os grupos. Nosso estudo sugere que a umidificação não tem impacto sobre o TMC nasal, as propriedades do muco, a inflamação e os sintomas em pacientes com baixo fluxo de oxigênio via cateter nasal (BFON)<br>Mucociliary clearance (MCC) is a basic defense mechanism of the respiratory system against respiratory infection. The efficiency of this defense mechanism depends on the mucus composition and mucus depth, on the cilia integrity and function and the mucus-cilia interaction. The aim of this study was investigate the long-term effects of low-flow oxygen via nasal catheter (NLFO) using dry oxygen (Dried-NLFO) or humidified oxygen (Humidified-NLFO) on nasal mucociliary clearance, mucus properties, inflammation and symptoms in patients with chronic hypoxemia requiring long-term domiciliary oxygen therapy ( > 15 hours/day). Eighteen patients (mean age of 68 years, 7 male, mean BMI of 26 kg/m2, 66% COPD, 60% hypertensive and former smokers) initiating NLFO were randomized to Dried-NLFO (n=10) or Humidified-NLFO (n=9). Patients were assessed at baseline and along 12 hours, 7 days, 30 days, 12 months and 24 months for nasal MCC using saccharine test, mucus properties by means of contact angle, inflammation using total number of cells and cytokines concentration in nasal lavage fluid as well as symptoms by SNOT-20 questionnaire. The most important airway symptom reported by patients at baseline was cough that improved after 7 days of oxygen therapy. In our study, nasal MCC prolonged significantly (40%) and similarly in both groups along the study. Nasal lavage showed increased proportions of neutrophils, goblet cells and epidermal growth factor concentration as decreases in macrophages, IFN-a lfa, IL-8 and IL-10 concentrations along the study. No changes in the proportion of ciliated cells, IL-6 and mucus contact angle were observed in both groups. Coughing and sleep symptoms significantly decreased similarly in both groups. Our study suggests that humidification does not impact on nasal MCC, mucus properties, inflammation and symptoms in patients using NLFO
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Utiyama, Daniela Mitiyo Odagiri. "Efeitos do tabagismo e da cessação do tabagismo nos mecanismos de defesa de via aérea, propriedades do muco e inflamação nasal." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5170/tde-19062017-124945/.
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O tabagismo é um problema mundial de saúde pública e é considerado a principal causa de morte evitável no mundo associado com câncer de pulmão, doença pulmonar obstrutiva crônica e infarto agudo do miocárdio. O tabagismo induz alterações morfológicas e funcionais no sistema respiratório. O transporte mucociliar (TMC) é um dos principais mecanismos de defesa do sistema respiratório que pode ser alterado com a fumaça e outros produtos do cigarro. O objetivo desse estudo foi avaliar os efeitos do tabagismo e da cessação do tabagismo no TMC nasal, nas propriedades do muco e sobre marcadores inflamatórios. Trinta e três indivíduos tabagistas foram incluídos no estudo após concordância com o termo de consentimento livre e esclarecido. O recrutamento de voluntários foi realizado na Faculdade de Medicina da Universidade de São Paulo (FMUSP) e no Ambulatório de Cessação do Tabagismo da Disciplina de Pneumologia do Hospital das Clínicas da FMUSP. As variáveis desfecho foram o TMC nasal analisado por meio do teste de trânsito da sacarina, as propriedades do muco por meio do ângulo de contato e da transportabilidade da tosse por alto fluxo e a quantificação de células inflamatórias e concentração de interleucinas (IL)-6 e IL-8 em lavado nasal. Vinte cessadores (idade média: 51 anos, 9 do sexo masculino) foram avaliados no tempo basal do estudo, 1o mês, 3o mês e 12o mês de cessação do tabagismo e 13 tabagistas (média de idade: 52 anos, 6 do sexo masculino) foram avaliados no tempo basal e 12 meses após o basal. As características demográficas, hábito tabágico inicial e morbidades de tabagistas e de cessadores foram similares. No tempo basal do estudo, os tabagistas e cessadores apresentaram disfunção do TMC nasal (17,9 ± 10,1 min e 17,4 ± 7,7 min, respectivamente, p=0,880). A cessação do tabagismo induziu melhora significativa do TMC nasal no 1o mês, 3º mês e 12o mês em 63%, 76% e 85% dos indivíduos, respectivamente. Somente aos 12 meses, foi possível observar melhora na transportabilidade do muco por alto fluxo (~ 23%), porém com aumento do número de macrófagos (2x) em lavado nasal. Não observamos alterações no ângulo de contato do muco e nas concentrações de citocinas em lavado nasal. Concluímos que a cessação do tabagismo induz melhora rápida no TMC nasal, porém melhora nas propriedades do muco foi observada somente após 12 meses de cessação do tabagismo<br>Smoking is a health problem in the world. It is considered a main cause of preventable death and is associated with lung cancer, chronic obstructive pulmonary disease and myocardium infarction. Smoking induces morphological and functional changes in the respiratory system. Mucociliary clearance (MCC) is one of the main defense mechanisms of the respiratory system that can be affected by smoke and other cigarette products. The aim of this study was to assess the effects of smoking and smoking cessation on nasal MCC, mucus properties and inflammatory biomarkers. Thirty three smokers were included in this study after agreement with the written informed consent. Subject´s recruitment was performed at Faculdade de Medicina da Universidade de São Paulo (FMUSP) and Ambulatório de Cessação do Tabagismo da Disciplina de Pneumologia do Hospital das Clínicas da FMUSP. The outcome variables were nasal MCC evaluated by saccharin transit test, mucus properties using contact angle and mucus transportability by high airflow and quantification of inflammatory cells number and interleukin (IL)-6 and IL-8 in the nasal lavage fluid. Twenty volunteers in the smoking cessation program (mean age: 51 years, 9 male) were assessed at baseline, month 1, month 3 and month 12 after of the smoking cessation and 13 smokers (mean age: 52 years, 6 male) were assessed at baseline and 12 months after baseline. Demographic characteristics, smoking history and morbidities were similar between the two groups. At baseline, smokers showed impaired nasal MCC (17.9 ± 10.1 min and 17.4 ± 7.7 min, respectively, p=0.880). Smoking cessation significantly improved nasal MCC at 1 month, 3 months and 12 months in 63%, 76% and 85% of the subjects, respectively. Only after 12 months of smoking cessation, improvement in mucus transportability by high airflow (~ 23%) was observed, however, with increased number of macrophages (2-fold) in nasal lavage fluid. No changes were observed in mucus contact angle and cytokines concentrations in nasal lavage fluid. We concluded that smoking cessation induces rapid improvement in nasal MCC, however, improvement in mucus properties were observed only after 12 months of smoking cessation
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Neto, Waldir Carreirão. "Efeito da toxina botulínica tipo A sobre a expressão de neuropeptídeos e o transporte mucociliar nasal em coelhos." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5143/tde-06112015-143800/.
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INTRODUÇÃO: A toxina botulínica tipo A (TXB-A) tem sido testada no tratamento da rinite, principalmente nos casos de rinite idiopática. Sugere-se que um estado de hiper-reatividade do nervo trigêmeo esteja envolvido na fisiopatologia da rinite idiopática. O nervo trigêmeo possui fibras sensitivas não mielinizadas tipo C (FSNMT-C) que contém os neuropeptídeos substância P (SP) e peptídeo relacionado ao gene da calcitonina (CGRP). O óxido nítrico (NO) produzido pelas enzimas óxido nítrico sintase (NOS) também está envolvido nesse processo de neurorregulação nasal. O transporte mucociliar, mecanismo primário de defesa do sistema respiratório, é formado pelo batimento ciliar e muco nasal, e esses componentes podem ser influenciados por diferentes neuropeptídeos e neurotransmissores presentes na mucosa nasal. OBJETIVO: O objetivo deste estudo foi avaliar o efeito da TXB-A sobre a expressão da SP, CGRP e óxido nítrico sintase neural (nNOS), além de sua influência sobre o transporte mucociliar nasal em coelhos. MÉTODOS: Coelhos machos saudáveis da linhagem Nova Zelândia foram divididos em dois grupos: o grupo tratamento recebeu TXB-A (25UI) na concha nasomaxilar (CNM) do lado direito e soro fisiológico a 0,9% (SF0,9%) na CNM esquerda. O grupo controle recebeu SF0,9% na CNM direita e nenhuma intervenção na CNM esquerda. Foram investigados os efeitos da TXB-A sobre a expressão da SP, CGRP e nNOS no tecido de CNM por meio da imuno-histoquímica. Para esta análise, dividiu-se o tecido em camada externa (CE, acima da membrana basal) e camada interna (CI, abaixo da membrana basal). Avaliou-se também a presença de apoptose celular, a frequência de batimento ciliar (FBC), o perfil histoquímico do muco nasal (glicoproteínas ácidas e neutras) e a espessura do epitélio (ESP-CE). RESULTADOS: Foi observado um aumento significativo na quantidade de células apoptóticas na CNM do grupo tratamento que recebeu TXB-A em comparação aos controles (p <= 0,001). A CNM do grupo tratamento que recebeu SF0,9% exibiu um aumento na quantidade de células apoptóticas na CI ao comparar com os controles (CNM SF0,9%, p=0,035) (CNM sem intervenção, p=0,022), e também um aumento da expressão de SP na CE em comparação aos controles (CNM SF0,9%, p=0,021) (CNM sem intervenção, p=0,040). A expressão de CGRP apresentou um aumento na CNM do grupo tratamento que recebeu TXB-A em comparação à CNM sem intervenção (p=0,008). A FBC, expressão de nNOS, perfil histoquímico do muco nasal e ESP-CE não apresentaram diferenças significativas. DISCUSSÃO: O aumento da expressão de CGRP e SP pode ter sido causado por inibição de sua exocitose vesicular pela TXB-A, levando ao seu acúmulo intracelular. Não foram observadas diferenças significativas na FBC ou perfil histoquímico do muco nasal, indicando que o aumento da expressão de CGRP e SP não foi associado à inflamação. O aumento da quantidade de células apoptóticas e da expressão de SP na CNM SF0,9% do grupo tratamento pode ter sido causado por um efeito central da TXB-A. CONCLUSÃO: A administração nasal de TXB-A aumentou a expressão de CGRP e SP, possivelmente por acúmulo intracelular por causa da inibição da sua exocitose, mas sem alterar a FBC e o perfil histoquímico do muco nasal<br>INTRODUCTION: Botulinum toxin type A (BoNT-A) has been assessed in the treatment of rhinitis, especially in cases of idiopathic rhinitis. Trigeminal hyper-responsiveness appears to be involved in the pathological process of idiopathic rhinitis. Trigeminal nociceptive type C unmyelinated sensory fibers contain the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP). Nitric oxide (NO) produced by the enzyme nitric oxide synthase (NOS) are also involved in this nasal neurorregulation process. The mucociliary clearance, primary defense system of the respiratory system, is composed by the ciliary beat and nasal mucus. These components can be influenced by different nasal neuropeptides and neurotransmitters. OBJECTIVE: The aim of this study was to evaluate the effect of BoNT-A on the expression of SP, CGRP and neural nitric oxide synthase (nNOS), and its influence on nasal mucociliary clearance in rabbits. METHODS: Healthy New Zealand male rabbits were divided into two groups: the treatment group was challenged with BoNT-A (25UI) in the right nasomaxillary turbinate (NMT) and saline (SF0.9%) in the left NMT. The control group received SF0.9% in the right NMT and no-intervention in the left NMT. We investigated the effects of BoNT-A on SP, CGRP and nNOS expression in the NMT tissue by immunohistochemistry. Each area of interest was subdivided into an internal layer (IL: below the basement membrane) and outer layer (OL: above the basement membrane) for analysis. It was also assessed signs of cellular apoptosis, ciliary beat frequency (CBF), mucus histochemical profile (acidic and neutral glycoproteins) and epithelial thickness (EP-TH). RESULTS: It was observed a significant increase in the amount of apoptotic cells in the BoNT-A-challanged NMT compared with controls (p <= 0.001). The NMT of treatment group which received only SF0.9% showed an increase in the amount of apoptotic cells in the IL compared with controls (NMT SF0.9%, p = 0.035) (NMT no-intervention, p = 0.022), and also an increase in the SP expression in the OL compared with controls (NMT SF0.9%, p = 0.021) (NMT no-intervention, p = 0.040). CGRP expression showed higher expression in the BoNT-A-challanged NMT compared with no-intervention NMT (p=0.008). The CBF, nNOS expression, mucus histochemical profile and EP-TH did not show significant differences. DISCUSSION: The increased CGRP and SP expression could be due to inhibition of vesicular exocytosis by BoNT-A, leading to CGRP and SP intracellular accumulation. No significant differences in CBF or mucus histochemical profile were observed, indicating that the increased CGRP and SP expression was not associated with inflammation. The increase in the amount of apoptotic cells and SP expression in the SF0.9% NMT of treatment group may be due to a central effect of BoNT-A. CONCLUSION: Nasal administration of BoNT-A increased SP and CGRP expression, possibly via inhibition of their release, but did not change the CBF or mucus profile
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Ahmed, Shahzada Khuram. "Angiogenesis in the nasal mucosa." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4032/.
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Nasal polyposis is a common disease affecting 2-4% of the general population. The aetiology and pathogenesis are far from clear. Recent publications have suggested up-regulation of several pro-angiogenic factors including VEGF. The aim of this study was to assess and quantify the degree of angiogenesis in nasal polyposis and to determine if angiogenesis was the driving force behind polyposis. We started by developing a novel triple stain to assess remodelling in the nasal mucosa. For the first time we were able to categorically refute the common belief of angiogenesis driven polyposis. We then carried out genomic studies and identified upregulation of genes controlling the cell cycle and apoptosis, suggesting cell turnover is an important part of the pathogenesis of nasal polyps. Our gene expression data was confirmed by TUNEL staining, indicating an increased level of apoptosis in nasal polyp tissue, counterbalancing the increased cell proliferation. Inflammatory genes are also upregulated, however the data collected so far cannot distinguish between different types of inflammatory response. We carried out proteomic studies using the lu minex system but this did not clarify the situation despite using matched samples that were used in the gene array. They highlight the protein differences occurring in the polyps themselves. We have shown chemoattractants for eosinophils & macrophages (which are found in polyps), and significantly in iNOS, which is novel.
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Lindbom, John. "Phospholipase A₂ expression in the human nasal mucosa /." Linköping : Univ, 2004. http://www.bibl.liu.se/liupubl/disp/disp2004/med864s.pdf.
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Calderon-Zapatal, Moises Antonio. "The nasal epithelium, atopy and inflammation." Thesis, Queen Mary, University of London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286273.
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Harries, Helen Elizabeth. "Antibodies in the nasal mucosa : implications for allergic rhinitis." Thesis, King's College London (University of London), 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582540.
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Allergic rhinitis is the outcome of an IgE-mediated allergic response in the nose. Previous studies of IgE produced by B-cells in the nasal mucosa of allergic rhinitis patients have shown an increased usage of the V H5 gene family, compared to the normal blood V H gene repertoire, which has been attributed to superantigen activity. Work reported in this thesis has been undertaken to investigate further how the antibody repertoire is shaped in allergic rhinitis. IgA-expressing B-cells in the nasal mucosa, from allergic and non-allergic donors, were also shown to have an increased usage of VH5 genes compared to the normal blood repertoire, suggesting the nasal environment favours VH5 expansion prior to allergy development. Somatic hypermutation patterns in VH5-Ca sequences were indicative of superantigen selection. FACS analysis of nasal turbinate cells with antibodies to S. aureus enterotoxins (SE) demonstrated TSST -1 + cells in allergic nasal tissue only. Incubation of nasal turbinate tissue with SEs appeared not to influence the VH-Cϵ repertoire in 24 hours, but SED + IL-4 may have inhibited VH-Cϵ transcription in allergic patients. Evidence of local antigen stimulation prior to SE incubation was evident in one of the patients; a large VH5 clonal family exhibiting extensive somatic hypermutation was present throughout the nasal turbinate. FACS sorting of Phl pl-binding plasma cells and single cell RT-PCR enabled cloning of a scFv fragment representing the V regions of a physiological, allergen-specific antibody expressed in allergic nasal mucosa. The scFv cloning protocol has also been applied to VH5 genes of interest, thus facilitating the study of their protein structure and function. This research increases the evidence for local, VH5-selecting, superantigen activity in the nasal mucosa and has developed a platform for further investigation of nasal antibody- superantigen / allergen interactions in allergic rhinitis.
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王敏 and Min Wang. "Control of vascular reactivity of the nasal circulation." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31241153.
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Wang, Min. "Control of vascular reactivity of the nasal circulation /." Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B22233222.
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Bai, Xue-Feng. "Modulation of experimental T cell autoimmunity in the nervous system with emphasis on nasal tolerance /." Stockholm, 1998. http://diss.kib.ki.se/1998ki/19980116baix.
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Brooks, Zachary Edward. "Mechanical Stresses on Nasal Mucosa Using Nose-On-Chip Model." Wright State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=wright1578492176817977.
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Dhamankar, Varsha Sudhir. "Cytochrome P450-mediated drug metabolizing activity in the nasal mucosa." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/1585.
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Pre-systemic elimination by local enzymatic degradation can play a key role in limiting the bioavailability of intranasally administered drugs. Despite remarkable advancement in the characterization of the nasal biotransformative enzymes, knowledge of the role of the nasal mucosa in limiting bioavailability of therapeutic agents is still inadequate. The aim of this work was to evaluate the expression and substrate biotransformation activity of cytochrome P450 enzymes in the nasal mucosa using bovine olfactory and respiratory explants as in vitro models.
Gene expression and localization of major CYP450 isoforms in the nasal mucosa were examined using RT-PCR and immunohistochemistry. The bovine nasal mucosa showed abundant expression of CYP2A6 and 3A4 genes whereas 1A1, 1A2, 2C9, and 2C19 isoforms were expressed at much lower levels. The CYP450 proteins were observed to be present in the epithelial layer and in submucosal glandular cells.
The diffusion of melatonin, a CYP1A2 substrate, and the appearance of 6-hydroxymelatonin, its primary metabolite, across bovine olfactory and respiratory explants was measured, and nasal olfactory and respiratory microsomal preparations were used to quantify the kinetic parameters for melatonin 6-hydroxylation. Results indicated that bovine olfactory and respiratory CYP450 isoforms were metabolically active towards melatonin metabolism, and the respiratory mucosa demonstrated the greatest melatonin 6-hydroxylation activity.
Numerical simulations were used to probe the effects of the relative magnitudes of the permeability coefficient and enzymatic parameters on net substrate mass transfer across nasal mucosal tissues. The simulations indicated that the concentration gradient of the drug coupled with its permeability coefficient were the most significant factors controlling the transport of drugs across the mucosal tissue. Enzymatic degradation decreased the flux of drugs across the mucosa and had the greatest impact on low permeability compounds.
The results from these studies show that the bovine nasal mucosa possesses significant metabolic activity, and the flux of a metabolically labile substrate across the nasal mucosa can be significantly reduced by its enzymatic degradation within the tissue. Use of kinetic modeling to characterize of the extent of biotransformation in the nasal mucosa enables the identification of metabolism-limited bioavailability of intranasally administered drug compounds.
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Al, Khafaji Ammar Sahib Abdulameer. "Understanding the uptake of polystyrene nanoparticles by the nasal mucosa." Thesis, University of Iowa, 2016. https://ir.uiowa.edu/etd/2176.
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Nanoparticles have many proposed advantages for use in nasal drug delivery systems. Nanoparticles can improve uptake and efficacy and lower toxicity compared to the drug alone. In order to study the transport behavior of nanoparticles across nasal tissues, the uptake of non-biodegradable, fluorescently-labeled, carboxylate-modified polystyrene nanoparticles was measured. These 40 nm particles are spherical in shape and loaded with fluorescein, a fluorescent dye that can be measured spectrophotometrically, to determine the number of particles that entered the nasal tissues. In order to identify the pathways involved in the uptake of these particles, different pharmacologic inhibitors were also included in the nanoparticle transport studies. The results indicate that the nanoparticles enter the nasal tissues using several endocytosis mechanisms, namely, macropinocytosis, clathrin-mediated endocytosis, and caveolin-mediated endocytosis. These findings suggest that more than one endocytic pathway is involved in the uptake process in the nasal tissues, and these multiple pathways may help to increase the total nanoparticle uptake in the nasal tissues.
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Tao, Qian. "Cellular localization and gene expression of epstein-barr virus in non-neoplastic nasal mucosa and nasal lymphoma /." Hong Kong : University of Hong Kong, 1996. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17538828.
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STRAPPAVECCIA, Silvia. "IMPIANTO AUTOLOGO DI CELLULE STAMINALI NOM (NASAL OLFACTORY MUCOSA) IN CANI PARAPLEGICI CRONICI [AUTOLOGOUS IMPLANT OF NASAL OLFACTORY MUCOSA (NOM) STEM CELLS IN CHRONIC PARAPLEGIC DOGS]." Doctoral thesis, Università degli Studi di Camerino, 2007. http://hdl.handle.net/11581/401897.
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La terapia delle lesioni spinali croniche dell'uomo rappresenta attualmente uno dei maggiori campi di interesse della ricerca scientifica. Tra le strategie sperimentali di ultima elaborazione, il trapianto di cellule staminali sta dimostrando notevoli potenzialita' per la cura di molte patologie del SNC. I modelli animali principalmente utilizzati per gli studi sperimentali sono i ratti, ma le dimensioni del midollo spinale in questa specie sono estremamente diverse da quelle dell'uomo, e le condizioni di laboratorio in cui i protocolli sperimentali vengono applicati sono molto differenti dalle condizioni accidentali delle lesioni umane. Il trauma spinale e' un'evenienza piuttosto frequente nel cane, ma molto spesso la terapia non viene effettuata precocemente o e' inefficace, cosi' da portare ad una condizione di paraplegia cronica. In questa specie l'eziopatogenesi delle lesioni e le dimensioni del midollo sono simili a quelle dell'uomo. Per tali ragioni il cane rappresenta un buon modello per lo studio delle terapie sperimentali nelle lesioni spinali croniche. Lo scopo del presente lavoro e' quello di verificare se l'impianto autologo di cellule staminali adulte di natura olfattoria sia in grado di ripristinare la deambulazione volontaria in cani paraplegici cronici. Sono stati inclusi nello studio 6 soggetti sottoposti alla nostra attenzione tra gennaio 2004 e dicembre 2005 per l'insorgenza di un grave trauma spinale compreso tra le vertebre T4 e L3. Trascorsi almeno due mesi dall'insorgenza della paraplegia, in ciascun cane e' stato effettuato il prelievo bioptico della mucosa nasale. Il campione e' stato quindi inviato nel laboratorio di riferimento, dove le cellule staminali sono state isolate e allestite su un apposito supporto. Nei mesi successivi tutti i 6 pazienti sono stati sottoposti all'impianto delle cellule autologhe, dopo esposizione chirurgica del segmento midollare leso e asportazione del tessuto cicatriziale. La fase post-operatoria e' stata dedicata all'esecuzione di intensi protocolli fisioterapici e di indagini cliniche e strumentali, finalizzate alla valutazione del recupero neurologico. I risultati ottenuti hanno evidenziato la presenza di un parziale ripristino delle capacita' deambulatorie in 3 soggetti, mentre i tracciati elettrofisiologici relativi ai Potenziali Evocati Somato-Sensoriali (PESS) non hanno subito alcuna variazione nel periodo successivo all'impianto. In un soggetto, deceduto spontaneamente per una patologia indipendente dalla condizione neurologica, e' stato possibile sottoporre il midollo spinale a valutazioni di tipo istologico e immunoistochimico. Queste hanno evidenziato la presenza, nel tratto midollare sede dell'impianto, di gruppi di neuroni-fibre dispersi all'interno di abbondante tessuto fibroso. Pur considerando l'esiguita' del numero dei soggetti inclusi nella ricerca, e in attesa di poter sottoporre ad indagini istologiche il midollo spinale di 5 di loro, si puo' concludere che l'impianto di cellule staminali di origine olfattoria nel midollo spinale di cani paraplegici cronici puo' presentare notevoli potenzialita' terapeutiche. The treatment of chronic spinal cord injuries in humans is, today, one of the most important fields of scientific research. Among the experimental strategies recently developed, stem cell transplants are demonstrating great potentiality for the cure of many central nervous system (CNS) pathologies. The most common animal models used in experimental studies are rats but the dimensions of the spinal cord of this species are quite different from those of the human, and the laboratory conditions in which the experimental protocols are applied do not resemble the accidental conditions of human injuries. Spinal cord injuries are relatively frequent in dogs but very often the therapy is not applied promptly or is not efficacious, and the result is a condition of chronic paraplegia. The etiopathogenesis of the injuries and the dimensions of the spine of the dog are similar to those of the human. For these reasons, the dog represents a good model for studying experimental treatment of chronic spinal cord injuries. The aim of this study is to verify whether the autologous implant of adult stem cells obtained from nasal olfactory mucosa (NOM) is able to restore voluntary ambulation in dogs with chronic paraplegia. This study concerns six subjects that we cared for between January 2004 and December 2005 after the onset of a serious spinal trauma in the area between the vertebrae T4 and L3. At least two months after the onset of paraplegia, a bioptic sample was taken from the nasal mucosa of each dog. The sample was sent to the reference laboratory where the stem cells were isolated and prepared on an appropriate scaffold. During the following months all six patients were subjected to the implant of autologous cells, after the surgical exposure of the injured segment of the spinal cord and the removal of scar tissue. The post-surgical phase was dedicated to intensive physiotherapy protocols and clinical and instrumental investigations, with the aim of evaluating the neurological recovery. The results obtained demonstrated the presence of a partial restoration of the ambulatory capacity in three subjects, while the electrophysiological pathways relative to the Somatosensory Evoked Potential (SSEPs) did not undergo any variation in the period following the implant. In the case of one dog, that died spontaneously from a pathology not connected with the neurological condition, it has been possible to carry out histological and immununohistochemical evaluations of the spinal cord. These have demonstrated the presence of groups of neuron-fibres dispersed inside abundant fibrous tissue in the area of the implant. While taking into consideration the small number of subjects included in the research and in anticipation of being able to subject the spinal cords of the other five dogs to histological investigations, we can nevertheless conclude that the implant of the stem cells of olfactory origin in the spinal cord of dogs with chronic paraplegia can offer outstanding therapeutic potential.
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Lee, Myong Gyong. "Studies of the impact of air-pollutant exposure on nasal mucosa /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2005. http://uclibs.org/PID/11984.
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Yoshida, Jony Takao. "Nanopartículas de quitosana como veículo de vacinação contra a hepatite B via nasal." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/9/9134/tde-15032013-163603/.
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A imunização por via nasal pode representar uma alternativa as imunizações intramusculares, pois a aplicação por essa rota não é invasiva e há fácil acesso da vacina à mucosa. Além disso, a mucosa nasal apresenta diversas características que podem favorecer a imunização, por exemplo, há uma grande área superficial altamente vascularizado disponível para a absorção dos antígenos. Outra característica fundamental é a capacidade da mucosa de responder a antígenos, através das células imunocompetentes presentes, como as células M e dendríticas. Apesar disso, outros métodos podem ser empregados para melhorar absorção e disponibilidade dos antígenos pela mucosa, como a utilização de polímeros biodegradáveis. Entre estes, a quitosana é um biopolímero, derivado da desacetilação da quitina, que tem como principal característica, a possibilidade de estrutura-los em nanopartículas. Outra característica importante é sua propriedade catiônica a qual possibilita a sua ligação a proteínas e também à mucosa, que provoca maiores taxas de retenção de antígenos pela mucosa. Assim, neste trabalho, foi avaliado a imunogenicidade da inoculação do antígeno de superfície da hepatite B (HBsAg), via mucosa nasal em camundongos, os quais produziram anticorpos IgG contra HBsAg, apresentaram aumento da secreção de IgA pela mucosa nasal, e também ao avaliar a resposta de citocinas em células RAW 264.7, houve secreção de TNF-α .<br>The nasal vaccination is not invasive since its do not require needles for your application and your administration for is easy, thus the immunization via nasal route could be an alternative to intramuscular immunizations. Furthermore, the nasal mucosa has several characteristics like highly vascularized surface area available for absorption of antigen that could elicited the mucosal immune response caused by the competents cell available on the mucosal tissue. Nevertheless, other methods can be employed to improve absorption and availability of antigens to the mucosa, such as the use of nanoparticles of chitosan. Chitosan is a biopolymer product of deacetylation reaction of chitin, that has as main characteristic, the moldability, which enables the production of nanoparticles and its cationic property which allows its binding to proteins and also to the mucosa, which would lead to higher rates of absorption of antigens through the nasal mucosa. Thus, this work investigated the immunogenicity of the administration nanoparticles of chitosan with the surface anti-gen of hepatitis B (HBsAg) via the nasal mucosa in mice, which show levels of IgA in nasal lavages and serum IgG, as well as cytokines such as TNF-α released by RAW 264.7 cells of mice.
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Bezerra, Thiago Freire Pinto. "O papel do biofilme na rinossinusite crônica com polipose nasossinusal." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5143/tde-01082012-135039/.
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Introdução: A patogenia da rinossinusite crônica com polipose nasossinusal não está completamente estabelecida e existem algumas explicações para essa doença como os superantigenos, o desequilíbrio inflamatório e, mais recentemente, o biofilme. Objetivos: Avaliar a associação entre a presença do biofilme e a presença de rinossinusite crônica com polipose nasossinusal. Avaliar o quadro clínico e radiológico pré-operatória e pós-operatória segundo a presença do biofilme. Métodos: Este é uma estudo realizado em um hospital terciário universitário. A primeira parte foi um estudo caso-controle com um grupo de 33 pacientes consecutivos com rinossinusite crônica com polipose nasossinusal submetidos a cirurgica endoscópica nasossinusal e um grupo controle de 27 pacientes submetidos a septoplastia para tratamento de obstrução nasal. As amostras da mucosa foram coletadas no intra-operatório para avaliação por microscopia eletrônica de varredura para determinar a presença do biofilme. A segunda parte foi um estudo prospectivo em que dados pré-operatórios e pós-operatórios foram registrados, incluindo avaliações padronizadas da qualidade de vida doença-específica relacionadas à obstrução nasal e à rinossinusite, da endoscopia nasal e da tomografia de cavidades paranasais. A análise estatísca foi realizada. Para todos os testes um p=0.05 foi considerado significativo. Resultados: Os biofilmes foram encontrados em 72.7% (24/33) dos pacientes com rinossinusite crônica com polipose nasossinusal e 48.1% (13/27) dos pacientes submetidos a septoplastia (Odd ratio=2.87, IC95% 0.9796-8.419, p=0.051). Este foi o primeiro estudo a analisar o efeito da presença do biofilme nos resultados pós-operatórios com medidas padronizadas de um grupo de pacientes apenas com rinossinusite crônica com polipose nasossinusal. O biofilme estava presente em 72.4% (21/29) dos pacientes que completaram o seguimento. Os pacientes com biofilmes apresentaram uma pior pontuação pré-operatória NOSE e Lund-Kennedy estatísticamente significativos, mas uma mediana semelhante na pontuação total do SNOT-20. Os pacientes com biofilme apresentaram uma melhor resultado na pontuação Lund-Kennedy (p=0.036). Estes pacientes apresentaram piores resultados no SNOT-20 e resultados similares quanto ao NOSE e o Lund-Mackay. Conclusão: Os biofilmes foram demonstrados presentes nos pacientes submetidos a cirurgia endoscópica funcional para rinossinusite crônica com polipose nasossinusal mas também nos controles. Embora a prevalência não tenha sido diferente significativamente, o intervalo de confiança extremamente amplo de 95%, que apenas cruza a unidade, sugere que uma diferença significativa pode ter sido perdida por causa do baixo poder estatístico e estudos futuros serão necessários. Os biofilmes estiveram relacionados com pior qualidade de vida doença-específica pré-operatória NOSE e avaliação endoscópica (Lund-Kennedy), e melhores resultados endoscópicos. Nossos resultados sugerem que nos pacientes com uma melhora clínica significativa após a cirurgia, o biofilme representou um papel mais predominante na fisiopatologia da doença. Neste subgrupo, a cirurgia provavelmente removeu a quantidade de biofilme necessária para restaurar o desequilíbrio inflamatório na mucosa<br>Introduction: The pathogenesis of chronic rhinosinusitis with nasal polyps is not completely established and there are some explanations for this disease, such as superantigens, inflammatory imbalance and, more recently, biofilms. Objective: Evaluate the association of biofilms presence and chronic rhinosinusitis with nasal polyps. Evaluate outcomes after sinus surgery for chronic rhinosinusitis with nasal polyps according to the presence of biofilms. Methods: This is a University based-tertiary care center study. The first part was a case-control study that evaluated a group of 33 consecutive patients undergoing functional endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps and a control group of 27 patients undergoing septoplasty for nasal obstruction treatment. Mucosal samples were harvested intra-operatively for scanning electron microscopic examination to determine biofilms presence. The second part was a prospective study. Preoperative and follow up data were recorded, including standardized evaluations of disease-specific quality of life related to nasal obstruction and rhinosinusitis, of nasal endoscopy and sinus computer tomography scan. Statistical analysis was performed. For all statistical tests p=0.05 was considered significant. Results: Biofilms were found in 72.7% (24/33) of chronic rhinosinusitis with nasal polyps patients and in 48.1%(13/27) of septoplasty patients (Odds ratio = 2.87, CI95% from 0.9796 to 8.419, p=0.051). This was the first report to analyze the effect of biofilms in outcomes with standardized measures of a group of only chronic rhinosinusitis with nasal polyps patients. Biofilms were present in 72.4% (21/29) of these patients. Patients with biofilms had a statistically significant worst preoperative score related to nasal obstruction and nasal endoscopy, but a similar median sinusitis total score. Patients with biofilms presented better Lund-Kennedy outcome (-3[5]vs.-1[2],U=46.0,p=0.036), but the best endoscopic improvement might reflect the worst clinical preoperative status. These patients had worst outcomes in SNOT-20 (-0.75[1.15]vs.-1.30[1.32],U=69.0,p=0.21) and similar outcomes in NOSE(-55.0[50.0] vs. -60.0[50.0], U=81.0,p=0.67) and Lund-Mackay (-4[5]vs.-4[4]),U=75.5,p=0.49). Patients with biofilms presented better Lund-Kennedy outcome (p=0.036). There was a correlation among some QoL outcome scores in both groups. Conclusion: Biofilms were demonstrated to be present in patients undergoing functional endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps but also in controls. Although the prevalence was not significantly different, the extremely wide 95% confidence interval, which just crosses unity, suggests that a meaningful clinical difference may have been missed because of low statistical power and that further study is necessary. Biofilms were related with worst preoperative disease-specific quality of life questionnaire (NOSE) and endoscopic evaluation (Lund-Kennedy), and better endoscopic outcome. Our findings suggest that in patients with a significant clinical improvement after surgery, the biofilm had a more predominant role in the pathophysiology of the disease. In this subgroup, the surgery probably removed the amount of biofilms needed to restore the mucosal inflammatory imbalance
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Carvalho, Flávia Chiva [UNESP]. "Sistemas nanoestruturados mucoadesivos para administração nasal de zidovudina." Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/102463.
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000701076.pdf: 1643903 bytes, checksum: 6b4257d60071e68223b49db2bbd28bff (MD5)<br>Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)<br>Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)<br>Universidade Estadual Paulista (UNESP)<br>A zidovudina (AZT) é o fármaco de primeira escolha no tratamento da AIDS, mas sofre metabolismo pré-sistêmico e possui efeitos adversos dose-dependentes. A via nasal é uma alternativa que pode promover a rápida absorção do fármaco e evitar o metabolismo pré-sistêmico. Porém, ela possui mecanismos de depuração mucociliar que pode eliminar rapidamente a formulação da cavidade nasal. Sistemas de liberação mucoadesivos podem aumentar a fixação da formulação, controlar e aumentar a absorção de fármacos através da mucosa nasal. Sistemas compostos por tensoativos podem formar estruturas líquido-cristalinas in situ e promover a mucoadesão. O objetivo deste trabalho foi desenvolver sistemas precursores de cristais líquidos compostos pelo tensoativo álcool cetílico etoxilado 20 OE e propoxilado 5 OP (PPG-5-CETETH-20) para administração nasal do AZT. O comportamento de fases dos sistemas foi investigado pela construção de diagramas de fases binários e ternários combinando o tensoativo com água e fosfatidilcolina ou ácido oleico. As amostras escolhidas foram caracterizadas por microscopia de luz polarizada (MLP), reologia, análise mecânica e de obtenção da força mucoadesiva utilizando texturômetro. Foram realizados estudos de permeação ex vivo e testes pré-clínicos em ratos. Os resultados mostram que é possível obter um sistema composto por PPG-5-CETETH-20/ ácido oleico/água com escoamento adequado para administração nasal e alta capacidade de solubilização do AZT. A mistura do sistema com muco artificial forma uma matriz líquido-cristalina com características reológicas, perfil de textura e força mucoadesiva adequados para promover a mucoadesão na cavidade nasal. O ensaio de permeação utilizando...<br>Zidovudine (AZT) is the first choice drug for AIDS treatment, but it undergoes presystemic metabolism and exhibits dose-dependent side effects. The nasal route is an alternative that promotes the rapid absorption of the drug and avoids its presistemic metabolism. However, the mucociliary clearance mechanism can rapidly eliminate the formulation from the nasal cavity. Mucoadhesive drug delivery systems may raise the fixation of the formulation, control and increase AZT absorption through the nasal mucosa. Systems composed of surfactants can form in situ liquid crystalline structures and promote the mucoadhesion. The objective of this work was to develop liquid crystal precursor systems composed of the surfactant polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol (PPG-5-CETETH-20) for the nasal administration of AZT. The phase behavior of the systems was investigated by the construction of binary and ternary phase diagrams combining the surfactant with water, phosphatidylcholine or oleic acid. The chosen samples were characterized by polarized light microscopy (PLM), rheology, and mechanical analysis and by obtation of the mucoadhesive force using a texturometer. It was performed ex vivo drug permeation studies and pre-clinical tests in rats. The results showed that it is possible to obtain a liquid system composed of PPG-5-CETETH-20/ oleic acid/ water with high capacity for AZT solubilization. The mixture of the system with artificial mucus forms a liquid crystalline matrix with suitable rheological characteristics, texture profile and mucoadhesive force for promoting the mucoadhesion in the nasal cavity. The permeation assay using porcine nasal mucosa showed that the formulation does not retain AZT release and increases the flux J (0.871 g/min.cm) and the permeability coefficient Kp... (Complete abstract click electronic access below)
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Carvalho, Flávia Chiva. "Sistemas nanoestruturados mucoadesivos para administração nasal de zidovudina /." Araraquara : [s.n.], 2012. http://hdl.handle.net/11449/102463.
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Orientador: Maria Palmira Daflon Gremião<br>Coorientador: Rosângela Gonçalves Peccinini<br>Banca: Sílvia Stanisçuaski Guterres<br>Banca: Marcos Luciano Bruschi<br>Banca: Marlus Chorilli<br>Banca: Beatriz Stringhetti Ferreira Cury<br>Resumo: A zidovudina (AZT) é o fármaco de primeira escolha no tratamento da AIDS, mas sofre metabolismo pré-sistêmico e possui efeitos adversos dose-dependentes. A via nasal é uma alternativa que pode promover a rápida absorção do fármaco e evitar o metabolismo pré-sistêmico. Porém, ela possui mecanismos de depuração mucociliar que pode eliminar rapidamente a formulação da cavidade nasal. Sistemas de liberação mucoadesivos podem aumentar a fixação da formulação, controlar e aumentar a absorção de fármacos através da mucosa nasal. Sistemas compostos por tensoativos podem formar estruturas líquido-cristalinas in situ e promover a mucoadesão. O objetivo deste trabalho foi desenvolver sistemas precursores de cristais líquidos compostos pelo tensoativo álcool cetílico etoxilado 20 OE e propoxilado 5 OP (PPG-5-CETETH-20) para administração nasal do AZT. O comportamento de fases dos sistemas foi investigado pela construção de diagramas de fases binários e ternários combinando o tensoativo com água e fosfatidilcolina ou ácido oleico. As amostras escolhidas foram caracterizadas por microscopia de luz polarizada (MLP), reologia, análise mecânica e de obtenção da força mucoadesiva utilizando texturômetro. Foram realizados estudos de permeação ex vivo e testes pré-clínicos em ratos. Os resultados mostram que é possível obter um sistema composto por PPG-5-CETETH-20/ ácido oleico/água com escoamento adequado para administração nasal e alta capacidade de solubilização do AZT. A mistura do sistema com muco artificial forma uma matriz líquido-cristalina com características reológicas, perfil de textura e força mucoadesiva adequados para promover a mucoadesão na cavidade nasal. O ensaio de permeação utilizando... (Resumo completo, clicar acesso eletrônico abaixo)<br>Abstract: Zidovudine (AZT) is the first choice drug for AIDS treatment, but it undergoes presystemic metabolism and exhibits dose-dependent side effects. The nasal route is an alternative that promotes the rapid absorption of the drug and avoids its presistemic metabolism. However, the mucociliary clearance mechanism can rapidly eliminate the formulation from the nasal cavity. Mucoadhesive drug delivery systems may raise the fixation of the formulation, control and increase AZT absorption through the nasal mucosa. Systems composed of surfactants can form in situ liquid crystalline structures and promote the mucoadhesion. The objective of this work was to develop liquid crystal precursor systems composed of the surfactant polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol (PPG-5-CETETH-20) for the nasal administration of AZT. The phase behavior of the systems was investigated by the construction of binary and ternary phase diagrams combining the surfactant with water, phosphatidylcholine or oleic acid. The chosen samples were characterized by polarized light microscopy (PLM), rheology, and mechanical analysis and by obtation of the mucoadhesive force using a texturometer. It was performed ex vivo drug permeation studies and pre-clinical tests in rats. The results showed that it is possible to obtain a liquid system composed of PPG-5-CETETH-20/ oleic acid/ water with high capacity for AZT solubilization. The mixture of the system with artificial mucus forms a liquid crystalline matrix with suitable rheological characteristics, texture profile and mucoadhesive force for promoting the mucoadhesion in the nasal cavity. The permeation assay using porcine nasal mucosa showed that the formulation does not retain AZT release and increases the flux J (0.871 g/min.cm) and the permeability coefficient Kp... (Complete abstract click electronic access below)<br>Doutor
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Pinto, Paulo Sérgio Alves Vera-Cruz. "Alterações na mucosa nasal provocadas pela pressão atmosférica, oxigénio e outros factores." Doctoral thesis, Instituto de Ciências Biomédicas Abel Salazar, 2008. http://hdl.handle.net/10216/19381.
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Pinto, Paulo Sérgio Alves Vera-Cruz. "Alterações na mucosa nasal provocadas pela pressão atmosférica, oxigénio e outros factores." Tese, Instituto de Ciências Biomédicas Abel Salazar, 2008. http://hdl.handle.net/10216/19381.
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Bejgum, Bhanu Chander. "Uptake and distribution of ultrafine nanoparticles and microemulsions from the nasal mucosa." Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/5713.
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Various colloidal delivery systems, including polymeric nanoparticles, metal colloids, liposomes, and microemulsions have been reported to enhance the delivery of therapeutic agents following intranasal administration. However, the mechanisms involved in the uptake of these nanomaterials, especially those in the ultrafine size ranges (diameter < 20 nm) through nasal mucosa and their subsequent biodistribution in the body are not well characterized. The objectives of this study address the knowledge gap regarding ultrafine nanoparticle transfer in the nasal mucosa by quantifying nanoparticle uptake and biodistibution patterns in the presence and absence of known inhibitors of endocytic processes.
The uptake of ~ 10 nm fluorescent quantum dots (QDs) was investigated by measuring the concentration of QDs following exposure to bovine respiratory and olfactory mucosal explants. An inductively coupled optical emission spectroscopy method was developed to measure the amount of QDs within the tissues. The results demonstrated that carboxylate-modified QDs (COOH-QDs) show ~2.5 fold greater accumulation in the epithelial and submucosal regions of the olfactory tissues compared to the respiratory tissues. Endocytic inhibitory studies showed that in respiratory tissues clathrin-dependent, macropinocytosis and caveolae-dependent endocytosis process were all involved in the uptake of COOH-QDs. Whereas in olfactory tissues, clathrin-dependent endocytosis was the major endocytic pathway involved in uptake of COOH-QDs. Additional energy-independent pathways appeared to also be active in the transfer of COOH-QDs into the olfactory mucosa. Interestingly, PEGylated quantum dots (PEG-QDs) of similar size ~15 nm were not internalized into the bovine nasal tissues.
In vivo fluorescence imaging was used to study the biodistribution of quantum dots following nasal instillation in mice. These studies showed that majority of COOH-QDs remain in the nasal tissues for relatively long periods of time (up to 24 h) whereas PEG-QDs showed no such accumulation. Biodistribution studies of gold nanoparticles (~15 nm) in mice using micro-CT showed that gold nanoparticles were transferred to the posterior turbinate region and a fraction of the administered dose distributed to regions in close proximity to the olfactory bulb. Both NIR imaging and micro-CT imaging were useful tools for visualization of in vivo nanoparticle distribution.
A diazepam-containing microemulsion (dispersed phase ~40 nm) was formulated to investigate the uptake mechanisms utilized for fluid-phase colloidal dispersions in the nasal mucosa. The resulting diazepam-containing microemulsion showed enhanced transfer of the drug into the bovine nasal respiratory and olfactory tissues. It is unclear if endocytosis of the fluid-phase nanodispersions played a role in drug absorption from the microemulsions in a manner similar to the uptake of solid-phase nanoparticles, however, since there was significant loss of the epithelial cell layer following exposure to the microemulsion formulation which likely altered the barrier properties of the epithelium.
These studies have increased the fundamental understanding of ultrafine nanoparticle uptake in the nasal tissues and the resulting nanoparticle biodistribution patterns. While ultrafine nanoparticles may have limited application in the development of efficient drug delivery systems, an understanding of the size-dependent and tissue-dependent processes responsible for the uptake of particulates into mucosal tissues will contribute to the rational development of nanoparticulate drug delivery strategies investigating the nasal and other routes of administration.
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Worley, George Anthony. "Cigarette smoke and nasal inflammation : an in vitro study." Thesis, Queen Mary, University of London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.420538.
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Abraão, Lígia Maria [UNESP]. "Detecção dos genes de virulência e identificação do perfil clonal de isolados de Staphylococcus aureus colonizantes de nasofaringe otbtidos em estudo de base populacional." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/110458.
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000747680.pdf: 2678639 bytes, checksum: e24657234d93469753d524eb03f006fd (MD5)<br>Estudos recentes apontam para elevação da incidência e da gravidade das infecções por Staphylococcus aureus. Esse fato é agravado pela ampla disseminação de isolados de Staphylococcus aureus resistentes à meticilina (MRSA) nos hospitais, além de sua recente introdução na comunidade. A colonização nasal de indivíduos assintomáticos é o principal fator responsável pela persistência e disseminação de S. aureus nas populações humanas. Assim sendo, inquéritos de carreamento nasal são importantes para estimar a “carga” (burden) de S. aureus como um todo e de MRSA na comunidade. Além disso, a compreensão da relação bactéria-hospedeiro e dos fatores de virulência envolvidos se faz necessária para o combate às infecções que colocam em risco a vida da população em geral. O presente trabalho teve como objetivo investigar a distribuição de clones de Staphylococcus aureus e MRSA na população da área urbana de Botucatu, SP, identificando a prevalência dos determinantes de virulência junto aos fatores de risco associados em isolados obtidos da nasofaringe de indivíduos hígidos do município. Um total de 223 amostras de S. aureus isoladas de secreções nasais foi submetido a testes de susceptibilidade antimicrobiana à oxacilina e cefoxitina através da técnica de discodifusão. O método de E-test foi empregado para determinar a Concentração Inibitória Miníma (CIM) em amostras resistentes. Em seguida, foram realizadas reações de PCR para a detecção dos genes mecA, genes codificadores de fatores de virulência das enterotoxinas (sea, seb e sec) e toxina associada à síndrome do choque tóxico (tst); toxinas esfoliativas A e B (eta, etb), leucocidina de Panton-Valentine (lukS-PV e lukF-PV), hemolisinas alfa e delta (hla e hld); e biofilme (icaA e icaD). A tipagem molecular para a determinação dos clusters foi realizada pela técnica de PFGE. Para avaliar os fatores ...<br>Recent findings show an increase on the incidence and severity of Staphylococcus aureus infection. This fact is worsened by the wide dissemination of the methicillin-resistant S. aureus (MRSA) isolates in hospitals and its recent introduction in the community settings. The nasal colonization in asymptomatic individuals remains the main factor responsible for the persistence and dissemination of S. aureus in the human population. Thereby, nasal carriage surveys are an important tool in order to estimate the total S. aureus burden and the MRSA in the community. Besides, understanding the bacterial-host relationship and the virulence factors involved is necessary in order to manage the infections that jeopardize the population’s health. The present study aims at investigating the clonal distribution of S. aureus and MRSA strains in an urban population area in Botucatu, SP, identifying both the prevalence of the virulence determinants together to the associated risk factors in samples obtained from the nasopharynx of healthy individuals from Botucatu. A total of 223 S. aureus samples isolated from nasal secretions were submitted to the antimicrobial susceptibility tests through the disk-difusion method with oxacillin and cefoxitin disks. The E-test method with oxacillin was applied in order to obtain the Minimum Inhibitory Concentration (MIC) among oxacillin disk resistant samples. Afterwards, PCR (Polimerase Chain Reaction) was carried out for the detection of the mecA gene and of the following virulence genes: enterotoxins (sea, seb and sec), toxic shock syndrome toxin (tst), exfoliative toxin A and B (eta, etb), Panton-Valentine Leukocidin (lukS-PV and lukF-PV), alphaand delta-hemolysins (hla and hld), and biofilms (icaA and icaD). The PFGE molecular typing was employed in order to determine the prevalent clusters. The univariate and multivariate linear regression was carried out so that the risk factors ...
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Abraão, Lígia Maria. "Detecção dos genes de virulência e identificação do perfil clonal de isolados de Staphylococcus aureus colonizantes de nasofaringe obtidos em estudo de base populacional /." Botucatu, 2013. http://hdl.handle.net/11449/110458.
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Orientador: Maria de Lourdes Ribeiro de Souza da Cunha<br>Coorientador: Carlos Magno Castleo Branco Fortaleza<br>Banca: Carlos Roberto Veiga Kiffer<br>Banca: Elizabeth Losshchagin Pizzolitto<br>Resumo: Estudos recentes apontam para elevação da incidência e da gravidade das infecções por Staphylococcus aureus. Esse fato é agravado pela ampla disseminação de isolados de Staphylococcus aureus resistentes à meticilina (MRSA) nos hospitais, além de sua recente introdução na comunidade. A colonização nasal de indivíduos assintomáticos é o principal fator responsável pela persistência e disseminação de S. aureus nas populações humanas. Assim sendo, inquéritos de carreamento nasal são importantes para estimar a "carga" (burden) de S. aureus como um todo e de MRSA na comunidade. Além disso, a compreensão da relação bactéria-hospedeiro e dos fatores de virulência envolvidos se faz necessária para o combate às infecções que colocam em risco a vida da população em geral. O presente trabalho teve como objetivo investigar a distribuição de clones de Staphylococcus aureus e MRSA na população da área urbana de Botucatu, SP, identificando a prevalência dos determinantes de virulência junto aos fatores de risco associados em isolados obtidos da nasofaringe de indivíduos hígidos do município. Um total de 223 amostras de S. aureus isoladas de secreções nasais foi submetido a testes de susceptibilidade antimicrobiana à oxacilina e cefoxitina através da técnica de discodifusão. O método de E-test foi empregado para determinar a Concentração Inibitória Miníma (CIM) em amostras resistentes. Em seguida, foram realizadas reações de PCR para a detecção dos genes mecA, genes codificadores de fatores de virulência das enterotoxinas (sea, seb e sec) e toxina associada à síndrome do choque tóxico (tst); toxinas esfoliativas A e B (eta, etb), leucocidina de Panton-Valentine (lukS-PV e lukF-PV), hemolisinas alfa e delta (hla e hld); e biofilme (icaA e icaD). A tipagem molecular para a determinação dos clusters foi realizada pela técnica de PFGE. Para avaliar os fatores ...<br>Abstract: Recent findings show an increase on the incidence and severity of Staphylococcus aureus infection. This fact is worsened by the wide dissemination of the methicillin-resistant S. aureus (MRSA) isolates in hospitals and its recent introduction in the community settings. The nasal colonization in asymptomatic individuals remains the main factor responsible for the persistence and dissemination of S. aureus in the human population. Thereby, nasal carriage surveys are an important tool in order to estimate the total S. aureus burden and the MRSA in the community. Besides, understanding the bacterial-host relationship and the virulence factors involved is necessary in order to manage the infections that jeopardize the population's health. The present study aims at investigating the clonal distribution of S. aureus and MRSA strains in an urban population area in Botucatu, SP, identifying both the prevalence of the virulence determinants together to the associated risk factors in samples obtained from the nasopharynx of healthy individuals from Botucatu. A total of 223 S. aureus samples isolated from nasal secretions were submitted to the antimicrobial susceptibility tests through the disk-difusion method with oxacillin and cefoxitin disks. The E-test method with oxacillin was applied in order to obtain the Minimum Inhibitory Concentration (MIC) among oxacillin disk resistant samples. Afterwards, PCR (Polimerase Chain Reaction) was carried out for the detection of the mecA gene and of the following virulence genes: enterotoxins (sea, seb and sec), toxic shock syndrome toxin (tst), exfoliative toxin A and B (eta, etb), Panton-Valentine Leukocidin (lukS-PV and lukF-PV), alphaand delta-hemolysins (hla and hld), and biofilms (icaA and icaD). The PFGE molecular typing was employed in order to determine the prevalent clusters. The univariate and multivariate linear regression was carried out so that the risk factors ...<br>Mestre
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Lourenço, Delaide Sampaio Dias. "Detecção da infecção subclínica de Mycobacterium leprae em menores de quinze anos, contactantes de hansenianos, Fortaleza - Ceará." reponame:Repositório Institucional da UFC, 2016. http://www.repositorio.ufc.br/handle/riufc/15519.
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LOURENÇO, Delaide Sampaio Dias. Detecção da infecção subclínica de Mycobacterium leprae em menores de quinze anos, contactantes de hansenianos, Fortaleza - Ceará. 2016. 97 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2016.<br>Submitted by denise santos (denise.santos@ufc.br) on 2016-03-16T15:09:39Z
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Previous issue date: 2016<br>Leprosy is an infectious disease caused by Mycobacterium leprae, obligate intracellular bacillus. Due to the increase in the incidence of new cases in juveniles under 15 years and the debilitating potential of the disease, especially in paucibacillary patients and neural forms, it is necessary to use detection tools of the presence of the bacillus, in order to diagnose the onset of the disease or subclinical infection detection contacts of cases. This study aimed to investigate the possibility of subclinical infection in contacts ≥5 and <15 years of new cases, detected in Dona Libania Dermatology Centre, in Fortaleza-Ceara. Participated in this study, 69 index cases and 101 contacts under 15 years. Until now, no study sought subclinical detection of contacts of new leprosy cases treated at a Reference Unit. The collected material was analyzed using three techniques: determination of bacterial index, according to the Procedural Guidelines of Bacilloscopy Technical Leprosy of the Ministry of Health-2010; molecular detection of M. leprae DNA in nasal secretion, collected with pre-humidified swabs in Tris-EDTA buffer. The DNA extraction was performed using the DNeasy Blood and Tissue Kit Qiagen, held at -20°C, for subsequent amplification. The RLEP-R1 e RLEP-R2 primers were used for the specific region RLEP. The PCR reaction occurred in a thermocycler using the kit Ilustra™ Pure Taq Ready-to-go PCR beads GE HEALTHCARE; ML-Flow analysis, immunoassay for the detection of IgM PGL-1, which was adopted collection technique of whole blood, making up a puncture on the right or left forefinger. Measuring the positivity of the three techniques used in the study, we obtained the frequencies of 16.1% for PCR DNA, 1.98% for bacterial index in nasal secretion and 33.7% for ML-Flow. The M. leprae DNA PCR combined with serology of anti-PGL-1 antibodies show how sensitive and specific tools, which can assist in monitoring contacts at greater risk of developing the disease, especially in childhood. The detection of M. leprae in the nasal mucosa reflects the presence of this site bacillus, which can become a source of infection or transmission. This information combined with the investigation of seropositivity anti-PGL-1 strengthen the diagnosis of subclinical infection, including the possibility of the presence of bacillus in other sites, for example, skin and/or nerves.<br>A hanseníase é uma doença infecto-contagiosa, causada pelo Mycobacterium leprae, bacilo intracelular obrigatório. Devido o aumento na incidência de casos novos em menores de 15 anos e ao potencial incapacitante da doença, principalmente em pacientes paucibacilares e com formas neurais, é necessário o emprego de ferramentas de detecção da presença do bacilo, visando ao diagnóstico no início da doença ou detecção de infecção subclínica em contactantes de casos. Este estudo teve como objetivo investigar a possibilidade de infecção subclínica nos contactantes ≥5 e <15 anos de casos novos, detectados no Centro de Dermatologia Dona Libânia, no município de Fortaleza-Ceará. Participaram deste estudo, 69 casos índices e 101 contactantes menores de 15 anos. Até o momento, nenhum estudo buscou a detecção subclínica da infecção em contatos de casos novos de hanseníase, atendidos em uma Unidade de Referência. O material coletado foi analisado através de três técnicas: determinação do Índice Baciloscópico, de acordo com o Guia de Procedimentos Técnicos de Baciloscopia em Hanseníase do Ministério da Saúde-2010; detecção molecular de DNA de M. leprae, em secreção nasal, colhidas com swabs previamente umedecidos em tampão Tris-EDTA. A extração do DNA foi realizada utilizando o Dneasy Blood and Tissue kit Qiagen, mantido a -20ºC, para posterior amplificação. Foram utilizados os iniciadores RLEP-R1e RLEP-R2 para a região específica RLEP. A reação de PCR ocorreu em termociclador utilizando o kit Ilustra™ Pure Taq Ready-to-go PCR beads GE HEALTHCARE; análise de ML-Flow, teste imunocromatográfico para a detecção da IgM para PGL-1, na qual foi adotada a técnica de coleta do sangue total, fazendo-se uma punctura no dedo indicador esquerdo ou direito. Avaliando a positividade das três técnicas usadas no estudo, obtivemos frequência de 16,1% para PCR de DNA, 1,98% para Índice Baciloscópico na secreção nasal e 33,7% para ML-Flow. A PCR de DNA de M. leprae aliada à sorologia de anticorpos anti-PGL-1 se mostram como ferramentas sensíveis e específicas, podendo auxiliar no monitoramento dos contatos com maior risco de desenvolver a doença, principalmente na infância. A detecção do M. leprae na mucosa nasal reflete a presença do bacilo neste sítio, que pode tornar-se uma fonte de infecção ou transmissão. Esta informação aliada à investigação da soropositividade ao anti-PGL-1 reforçam o diagnóstico de infecção subclínica, inclusive com a possibilidade da presença do bacilo em outros sítios, como por exemplo, pele e/ou nervos.
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Shaida, Azhar Mohammed. "Matrix metalloproteinases and their inhibitors in the nasal mucosa in perennial allergic rhinitis." Thesis, Queen Mary, University of London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406469.
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Eriksson, Catarina. "Herbicide-induced toxicity in the nasal olfactory mucosa : studies on dichlobenil and chlorthiamid /." Uppsala : Sveriges lantbruksuniv, 1995. http://epsilon.slu.se/avh/1995/91-576-4881-6.gif.
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Chen, Nan. "Size and surface properties determining nanoparticle uptake and transport in the nasal mucosa." Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/1562.
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Gulbransen, Brian D. "Nasal solitary chemoreceptor cells : cell turnover, nerve dependence, and detection capabilities /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
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Thesis (Ph.D. in Neuroscience) -- University of Colorado Denver, 2007.<br>Typescript. Includes bibliographical references (leaves 129-151). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
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Karlson, Tanya De L. "Regulation of mucosal inflammation by fibroblasts /." Göteborg : Department of Microbiology and Immunology, Göteborgs universitet, 2007. http://hdl.handle.net/2077/3328.
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Palm, Jörgen. "Nasal airway nitric oxide : methodological aspects and influence of inflammation /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-801-7/.
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Mohammed, Nadeem K. "DIET, BACTERIA AND INFLAMMATION: THE INTESTINAL MUCOSA AND METABOLIC SYNDROME." UKnowledge, 2012. http://uknowledge.uky.edu/nutrisci_etds/4.
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Long term consumption of a high fat diet (HFD) increases the risk of developing Metabolic Syndrome and type 2 diabetes. This led us to hypothesize that long term HFD consumption impairs immune tolerance to the intestinal bacteria. Our studies had two goals. First, we characterized the effect of long term HFD consumption on the systemic immune response by comparing C57BL6 mice fed a HFD and low fat diet (LFD). Plasma immunoglobulin G (IgG) against Escherichia coli (LF-82), E. coli (Nissle 1917), Bacteroides thetaiotaomicron and Lactobacillus acidophilus were measured by a lab-developed ELISA. Fasting blood glucose and inflammation were measured in LFD mice and HFD mice. To test whether our findings were clinically relevant, anti-bacterial IgG and TNF-α were measured in plasma samples from lean healthy individuals, obese non-diabetics and obese diabetics. Our second aim was to investigate the relationship between HFD consumption and intestinal immunity. The effect of HFD consumption on immune responses in the GI tract was assessed by measuring fecal IgA levels in HFD mice and LFD mice. HFD mice had higher plasma IgG against the LF82 strain of Escherichia coli as well as higher plasma TNF-α, neutrophil percentage and fasting blood glucose levels. Obese diabetics had higher plasma IgG against the LF82 strain of E. coli than lean healthy controls. Studies on the effect of HFD on intestinal immunity revealed that HFD mice had lower fecal IgA than LFD mice. Our findings are novel in that they show an association between long term HFD consumption, systemic inflammatory immune responses to pathogenic intestinal bacteria and insulin resistance. These studies also showed that HFD consumption may impair intestinal immunity.
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Mendonça, Ullyanov Bezerra Toscano de. "Análise de mutações do gene KIT em pacientes com melanoma de mucosa de cabeça e pescoço e relação clínica retrospectiva." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5132/tde-14122015-114016/.
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Introdução: O melanoma mucoso de cabeça e pescoço (MMCP) é mais agressivo do que o melanoma cutâneo, marcadores prognósticos desta patologia não foram completamente esclarecidos devido a sua raridade. Em recentes estudos, algumas vias moleculares foram descritas na fisiopatologia destes tumores. Entre estas vias, existe a via da MAPK (Mitogen Activated Protein Quinase). Esta via de sinalização está envolvida no controle do crescimento celular, proliferação e migração, com um papel no desenvolvimento e progressão do melanoma. Além disso, a mutação do gene KIT foi identificada em melanomas, indicando a possibilidade de benefícios terapêuticos com o uso dos inibidores de tirosino-quinase. Objetivos: descrever a prevalência e características de mutações ativadoras do gene KIT em 28 pacientes com MMCP tratados no Instituto Nacional do Câncer-INCa; avaliar a relação entre a presença de mutação ativadora do gene KIT e evolução clínica dos pacientes tratados em relação ao estadiamento, sobrevida livre de doença e sobrevida global. Métodos: Estudo retrospectivo de coorte, foram incluídos 28 pacientes com MMCP tratados no INCA, entre 1998 e 2009. Foram analisados: estadiamento, tratamento primário, sobrevida livre de doença (SLD) e sobrevida global (SG). As curvas de sobrevida foram analisados utilizando o método de Kaplan-Meier, com software SPS 11.0. Análise KIT: O DNA foi extraído a partir de tecido incluído e fixado em parafina. O procedimento consiste de múltiplas etapas de desparafinização com xilol. Os restos celulares são precipitados por centrifugação e o DNA, no sobrenadante é utilizado nas reações de PCR (direto ou diluído). A análise mutacional do gene foi realizada utilizando-se a amplificação por PCR seguida pelo sequenciamento genômico. As análises são iniciadas pelo éxon 11, seguidas do éxon 9, 17 e 13. Resultados: Os pacientes eram predominantemente do sexo feminino (57%). A idade de apresentação variou de 27 a 85 anos. A região nasossinusal foi o sítio primário mais frequente (75%). Todos os pacientes foram submetidos a ressecção cirúrgica. Dezessete pacientes receberam radioterapia adjuvante (37%). As recorrências ocorreram em 82% dos pacientes. Presença de mutação de KIT foi encontrada em 7 casos (25%), três no éxon 9, 3 no éxon 11 e 1 no éxon 13. Fatores preditivos de recorrência foram índice mitótico (p = 0,05), invasão vascular (p = 0,043), e a disseminação perineural (p = 0,034). Não houve diferenças significativas na SLD e SG de acordo com a mutação KIT. Conclusão: A presente série incluiu 28 casos tratados. Sete casos (25%) tinham mutações ativadoras KIT. Esta descoberta sugere que existe um grupo de pacientes que poderiam se beneficiar com a terapia-alvo adequado com inibidores de tirosino-quinase<br>Unlike their cutaneous counterparts, head and neck mucosal malignant melanomas (HNMM) behave much more aggressively and their prognostic markers have not been fully elucidated. In recent studies, some molecular pathways have been found to be involved in the pathogenesis of melanomas. Among these, there is a proliferative MAPK pathway (\"Mitogen Activated Protein Kinase\"). This signaling pathway is involved in controlling cell growth, proliferation and migration, with a role in the development and progression of melanoma. In addition, KIT gene mutation has been identified in melanomas, indicating that there may be potential therapeutic benefits of tyrosine kinase inhibitors. Objectives: Evaluation of KIT mutation prevalence in a subset of 28 patients with HNMM treated at a single institution, establishing the relationship between different mutations and outcome (DFS and OS). The primary end-point of the study was to define the incidence of KIT mutations in HNMM, including the relationship between KIT mutations with disease-free survival (DFS) and overall survival (OS) in HNMM. Secondary end-points were correlation among therapeutic options, histopathological findings, demographic data and clinical response. Methods: This retrospective study comprised data of 28 patients with HNMM treated at Brazilian National Cancer Institute (INCA) between 2000 and 2011. Clinical analysis included patients characteristics, staging, primary and palliative treatments, disease free survival and overall survival. Progression-free survival and overall survival were analyzed using the Kaplan-Meier method, with SPS 11.0 software. KIT analysis: paraffin blocks were selected following analyses of histologic preparations, enabling DNA extraction. Different DNA concentrations were employed in PCR amplifications, based on DNA integrity. PCR amplification of exon, 9, 11, 13 and 17 was performed. . Results: Patients were predominantly females (57%). The age of presentation ranged from 27 to 85 years. The sinonasal region was the most frequent primary site (75%). All patients underwent surgical resection. Seventeen patients received adjuvant radiotherapy (37%). Recurrences occurred in 82% patients. Oncologic mutations in KIT were found in 7 (25%) of seven tumors, 3 in exon 9, 3 in exon 11 and 1 in exon 13. Predictive factors for recurrence were mitotic rate (p=0.05), vascular invasion (p=0.043), and perineural spread (p=0.034). There were no significant differences in DFS and OS according to KIT mutation. Conclusion: HNMM remains a rare disease. The present single-institution series includes 28 cases treated in single institution. Seven cases (25%) had activating KIT mutations, which is an increased prevalence of activating KIT mutations in this specific subset of mucosal melanomas. This finding suggests that there is a group of patients who might benefit with appropriate targeted therapy with kinase inhibitors
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Cameron, Elizabeth Anne. "Local isotype switching to IgE within allergic nasal mucosa in response to allergen exposure." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0035/NQ64528.pdf.
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Fransén, Nelly. "Studies on a novel powder formulation for nasal drug delivery /." Uppsala : Acta Universitatis Upsaliensis Acta Universitatis Upsaliensis, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9292.
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Salgado, Daniel Cauduro. "Distribuição de colágeno na concha nasal inferior de pacientes com rinite alérgica ou idiopática." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5143/tde-12012015-104722/.
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INTRODUÇÃO: Embora seja reconhecida a existência do espessamento da membrana basal e da fibrose da concha nasal na rinite alérgica, não há estudos descritivos do comportamento da mucosa nasal nos pacientes com rinite idiopática. O propósito desse estudo é descrever possíveis alterações na membrana basal e na lâmina própria da concha nasal inferior em pacientes com rinite alérgica ou idiopática, além do estudo quantitativo das fibras colágenas nesta localização. MÉTODOS: Analisou-se na concha nasal inferior obtida através de turbinectomia bilateral em 28 pacientes - 14 com rinite alérgica e 14 com rinite idiopática - a área ocupada pelo colágeno, a espessura da membrana basal e o diâmetro das fibrilas de colágeno através do uso de microscopia óptica (coloração Hematoxilina-eosina e Picrossírius-hematoxilina), microscopia eletrônica e imunoistoquímica para laminina e colágeno IV. RESULTADOS: 1) pacientes com rinite alérgica apresentaram significantemente maior área da concha nasal ocupada por colágeno do que o grupo com rinite idiopática. 2) a membrana basal de pacientes com rinite alérgica foi significantemente mais espessa. 3) a lâmina reticular da membrana basal dos pacientes com rinite alérgica apresentaram fibrilas de colágeno com menor diâmetro que os pacientes com rinite idiopática. 4) não houve diferenças significativas entre os grupos na distribuição de laminina e de colágeno IV. CONCLUSÕES: Alterações na mucosa nasal ocorrem na rinite alérgica, sendo caracterizadas pelo aumento da espessura da membrana basal e por fibrose. Na rinite idiopática, observou-se uma mucosa com aspecto estrutural semelhante aos pacientes normais<br>INTRODUCTION: Despite our knowledge about nasal conchae fibrosis and basement membrane thickening in allergic rhinitis, there are no descriptive studies on nasal mucosa behavior in patients with idiopathic rhinitis. The aim of our study was to describe possible changes in the basement membrane and lamina propria of the inferior concha in patients with idiopathic or allergic rhinitis, in addition to a quantitative study of collagen fibers in this site. METHODS: The inferior nasal concha obtained from 28 patients submitted to bilateral turbinectomy was examined - 14 with allergic rhinitis and 14 with idiopathic rhinitis; analyzing the collagen area, the basement membrane thickness and the collagen fibrils diameter using optical microscopy (Hematoxylin-eosin and Picrosirius-hematoxylin staining), electron microscopy and immunohistochemistry for laminin and collagen IV. RESULTS: 1) patients with allergic rhinitis had a significantly larger area of the nasal concha occupied by collagen than the group with idiopathic rhinitis. 2) the basement membrane of patients with allergic rhinitis was significantly thicker. 3) the reticular lamina of the basement membrane of patients with allergic rhinitis had collagen fibrils with diameters which were smaller than those from patients with idiopathic rhinitis. 4) there were no significant differences between the groups concerning the distribution of laminin and collagen IV. CONCLUSIONS: Alterations to the nasal mucosa that happen in allergic rhinitis are characterized by basement membrane thickening and fibrosis. In idiopathic rhinitis the patients\' mucosae were structurally similar to those from normal patients
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Espefält, Westin Ulrika. "Olfactory Transfer of Analgesic Drugs After Nasal Administration." Doctoral thesis, Uppsala universitet, Institutionen för farmaci, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7829.
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Nasal administration of analgesics for achieving rapid pain relief is currently a topic of great interest. The blood-brain barrier (BBB) restricts access to the central nervous system (CNS) for several central-acting drugs, such as morphine and dihydroergotamine, which results in a substantial effect delay. Evidence for the olfactory transfer of drugs from the nasal cavity to the CNS after nasal administration, bypassing the BBB, is available for both animals and humans. The aims of this thesis were to study the olfactory transfer of morphine to the CNS after nasal administration, and to compare the nasal transport of analgesic drugs across nasal respiratory and olfactory mucosa. In vivo studies in rodents demonstrated that morphine is transferred via olfactory pathways to the olfactory bulbs and the longitudinal fissure of the brain after nasal administration. Further, olfactory transfer of morphine significantly contributed to the early high morphine brain hemisphere concentrations seen after nasal administration to rats. Olfactory transfer was tracked by collecting and analysing brain tissue and blood samples after right-sided nasal administration and comparing the results to the situation after i.v. administration. The olfactory transfer was also visualised by brain autoradiography. In vitro studies indicated that the olfactory mucosa should not be a major barrier to the olfactory transfer of dihydroergotamine or morphine, since transport of these drugs was no more restricted across the olfactory mucosa than across the nasal respiratory mucosa. The in vitro studies were performed using the horizontal Ussing chamber method. This method was further developed to enable comparison of drug transport across nasal respiratory and olfactory mucosa which cannot be achieved in vivo. In conclusion, these analgesic drugs showed potential for olfactory transfer, and access to the CNS by this route should be further investigated in humans, especially for the drugs with central effects that are currently under development for nasal administration.
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Custódio, Luiz Antonio. "Avaliação da técnica de PCR na detecção de mycobacterium leprae em raspado de mucosa nasal." Universidade Estadual de Londrina. Centro de Ciências Biológicas. Programa de Pós-Graduação em Microbiologia, 2005. http://www.bibliotecadigital.uel.br/document/?code=vtls000110886.
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A hanseníase, doença debilitante, deformante e com elevado apelo social, causada pelo Mycobacterium leprae é um sério problema de saúde pública no Brasil e em outras regiões do mundo. A complexidade deste microrganismo tem desafiado os estudiosos durante anos. As novas técnicas de biologia molecular, como o PCR e seus avanços, podem permitir uma melhor compreensão e controle desta praga que assola a espécie humana há milhares de anos. Descrevemos uma técnica de next-PCR para amplificar uma seqüência do gene lsr2 do M. leprae com 100% de especificidade com um limite de detecção de 30 fg de DNA padrão. Foi detectado presença de DNA do M. leprae na mucosa nasal de 41,2% dos pacientes com hanseníase tuberculóide, 7,2% dos pacientes com hanseníase indeterminada e em 23,1% dos contatos.<br>Leprosy, a debilitating and deforming disease, with a high social impact, is still a very serious public health problem in Brazil and in other countries of the world. The complexity of the interactions between its causative agent Mycobacterium leprae and its host has defied research for tens of years, but now the modern techniques of molecular biology might allow a better understanding and control of this longstanding disease. We applied next PCR to amplify one sequence of the lsr2 gene of M. leprae, obtaining 100% of specificity for M. leprae, with a limit of detection of about 30fg of standardized DNA. With this technique, we detected the presence of M.leprae in the nasal mucus of 41.2% of patients with tuberculoid leprosy, 7.2% of patients with indeterminate leprosy, and 23.1% of contacts.
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Xavier, Rafaella Fagundes [UNESP]. "Transporte mucociliar em fumantes participantes de um programa de cessação do tabagismo." Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/87303.
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xavier_rf_me_prud.pdf: 788260 bytes, checksum: 7ab87eb37bf3e7b481df9e653a6f0f74 (MD5)<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)<br>Introdução: A exposição ao cigarro promove alterações que prejudicam a eficácia do transporte mucociliar. Contudo, a influência da intensidade de exposição, assim como os efeitos da abstinência ao tabagismo sobre essas alterações foram pouco elucidados. Objetivos: Avaliar a influência de diferentes intensidades de exposição ao cigarro sobre o transporte mucociliar e o efeito da cessação do tabagismo sobre o transporte mucociliar nasal em fumantes avaliados durante um período de 180 dias. Casuística e Métodos: Participantes de um programa de cessação ao tabagismo, foram avaliados quanto ao histórico tabagístico, ao nível de dependência à nicotina, à avaliação da função pulmonar (espirometria), a concentração de monóxido de carbono no ar exalado (COex), ao nível de carboxihemoglobina (COHb) e ao transporte mucociliar (tempo de trânsito de sacarina – TTS). Para comparação foi avaliado um grupo...<br>Introduction: Exposure to cigarette smoke promotes changes that harm the effectiveness of the mucociliary clearance. However, the influence of the intensity of exposure, as well as the effects of abstinence from smoking on these changes is poorly understood. Objectives: To assess the influence of different intensities of exposure to cigarette smoke on mucociliary clearance and the effect of cessation of smoking on nasal mucociliary clearance in smokers evaluated over a period of 180 days. Methods: Participants from a smoking cessation programme, were evaluated about smoking behavior, level of nicotine dependence, lung function (spirometry), the carbon monoxide in exhaled air (exhaled CO), the carboxyhemoglobin (COHb) and mucociliary clearance (saccharin transit time - STT). Was evaluated for comparison... (Complete abstract click electronic access below)
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Xavier, Rafaella Fagundes. "Transporte mucociliar em fumantes participantes de um programa de cessação do tabagismo /." Presidente Prudente : [s.n.], 2011. http://hdl.handle.net/11449/87303.
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Orientador: Ercy Mara Cipulo Ramos<br>Banca: Dionei Doffinger Ramos<br>Banca: Mariangela Macchione<br>Resumo: Introdução: A exposição ao cigarro promove alterações que prejudicam a eficácia do transporte mucociliar. Contudo, a influência da intensidade de exposição, assim como os efeitos da abstinência ao tabagismo sobre essas alterações foram pouco elucidados. Objetivos: Avaliar a influência de diferentes intensidades de exposição ao cigarro sobre o transporte mucociliar e o efeito da cessação do tabagismo sobre o transporte mucociliar nasal em fumantes avaliados durante um período de 180 dias. Casuística e Métodos: Participantes de um programa de cessação ao tabagismo, foram avaliados quanto ao histórico tabagístico, ao nível de dependência à nicotina, à avaliação da função pulmonar (espirometria), a concentração de monóxido de carbono no ar exalado (COex), ao nível de carboxihemoglobina (COHb) e ao transporte mucociliar (tempo de trânsito de sacarina - TTS). Para comparação foi avaliado um grupo... (Resumo completo, clicar acesso eletrônico abaixo)<br>Abstract: Introduction: Exposure to cigarette smoke promotes changes that harm the effectiveness of the mucociliary clearance. However, the influence of the intensity of exposure, as well as the effects of abstinence from smoking on these changes is poorly understood. Objectives: To assess the influence of different intensities of exposure to cigarette smoke on mucociliary clearance and the effect of cessation of smoking on nasal mucociliary clearance in smokers evaluated over a period of 180 days. Methods: Participants from a smoking cessation programme, were evaluated about smoking behavior, level of nicotine dependence, lung function (spirometry), the carbon monoxide in exhaled air (exhaled CO), the carboxyhemoglobin (COHb) and mucociliary clearance (saccharin transit time - STT). Was evaluated for comparison... (Complete abstract click electronic access below)<br>Mestre
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Rodrigues, Fernanda Maria Machado. "Tabagismo e mecanismos de defesa : resposta imune e transporte mucociliar /." Presidente Prudente, 2012. http://hdl.handle.net/11449/87308.
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Orientador: Ercy Mara Cipulo Ramos<br>Banca: Dionei Ramos<br>Banca: Renata Calciolari Rossi e Silva<br>Resumo: Introdução: O tabagismo é uma pandemia que causa inúmeros malefícios à saúde, dentre eles estão o aumento da inflamação sistêmica e o prejuízo do transporte mucociliar. Ambos colaboram para o aumento da frequência ou da severidade de infecções respiratórias em indivíduos com e sem doenças pulmonares crônicas tabaco relacionadas. A cessação tabagística é capaz de trazer benefícios, mas não se está bem estabelecido o comportamento dos marcadores inflamatórios nesta condição. Além disso, os efeitos da intensidade tabagística no prejuízo do transporte mucociliar também não foram completamente elucidados. Objetivo: Avaliar o comportamento sistêmico e local de marcadores inflamatórios em 30 dias de abstinência tabagística além dos efeitos das intensidades de consumo tabagístico no transporte mucociliar de tabagistas ativos. Métodos: Foram avaliados tabagistas participantes de um Programa de cessação... (Resumo completo, clicar acesso eletrônico abaixo)<br>Abstract: Introduction: Smoking is a pandemic that causes numerous health hazards, including increased systemic inflammation, impaired mucociliary clearance and increased frequency or severity of respiratory infections in individuals with and without chronic lung diseases related to tobacco. Smoking cessation can bring benefits, but is not well established the inflammatory markers' behavior at such condition. Besides that, the effects of the cigarette consumption intensity on impairment of mucociliary clearance have not been fully investigated. Aim: To evaluate the systemic and local behavior of the inflammatory markers at 30 days of smoking abstinence besides the effects of tobacco consumption intensities on mucociliary clearance of active smokers. Methods: We evaluated smokers participating in a smoking cessation program, who were... (Complete abstract click electronic access below)<br>Mestre
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Kölbeck, Karl-Gustav. "Nasal and bronchial airway reactivity in allergic and non allergic airway inflammation /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-428-3/.
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Yoskovitch, Adi. "Analysis of human papillomavirus in Schneiderian papillomas as compared to chronic sinusitis and normal nasal mucosa." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=31561.
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Schneiderian papillomas (SP) are tumors arising from the surface epithelium (Schneiderian epithelium) of the nasal cavity and paranasal sinuses. Evidence points towards a viral etiology, specifically Human papillomavirus (HPV). Although substantial data indicates HPV as a likely etiology, little is known about the role of HPV in benign nasal pathologies or in normal nasal mucosa. Objective. To characterize the role of HPV in SP, chronic sinusitis (CS) and its prevalence in normal nasal mucosa. A case controlled study was undertaken, matching patients with SP to patients with chronic sinusitis (CS). Patients with normal nasal mucosa served as a control group. All patients had their tissues analyzed for the presence of various HPV types using polymerase chain reaction (PCR) coupled with a line blot assay. Results. A total of 168 patients were identified (74 SP, 74 CS, 20 control). Of these, 70 (41.7%) had detectable DNA, and 9/70 (12.9%) had detectable HPV of types 6, 11, and 16. None had detectable HPV type 18. Significant differences were detected in the presence of HPV in CS, SP and control groups, as well as in the presence of low risk versus high-risk types amongst investigation and control groups. Conclusions. Significant differences exist in the distribution of HPV between SP, benign nasal pathologies such as CS and normal nasal mucosa. HPV may play an important role, at least as cofactor, in the development of SP, with types 6, 11 and 16 more pivotal than other types. Line blot assay may provide a useful technique in identifying HPV in SP.
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Procianoy, Elenara da Fonseca Andrade. "Teste da medida da diferença de potencial nasal transepitelial." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2014. http://hdl.handle.net/10183/119421.
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O teste da diferença de potencial nasal (DPN) é um exame que mede a diferença bioelétrica através do epitélio nasal, a qual resulta do transporte iônico transepitelial dos íons sódio (Na+), pelo canal ENaC (Epitelial Na+ Channel), e cloro (Cl-), pelo canal CFTR(Cystic Fibrosis Transmembrane Conductance Regulator). DPN tem sido utilizada como teste de auxilio diagnóstico em doenças associadas à disfunção do CFTR, como a Fibrose Cística (FC). FC é uma doença genética autossômica recessiva causada por mutações que afetam o funcionamento do canal CFTR (e secundariamente do ENaC) e levam a manifestações em diversos órgãos. Normalmente a dosagem de cloro no suor acima de 60 mEq/L ou a identificação de mutações nos dois alelos confirmam diagnóstico de FC. Porém, existem casos atípicos com exames considerados inconclusivos onde as características eletrofisiológicas decorrentes da disfunção do CFTR devem ser demonstradas para estabelecimento do diagnóstico. A identificação correta destes casos é importante para instituição do tratamento adequado e definição do prognóstico. O objetivo principal deste trabalho foi padronizar a técnica da DPN para sua futura aplicação como ferramenta diagnóstica através da determinação dos seus valores de referência, de sensibilidade, de especificidade e de concordância entre os resultados das duas narinas. Secundariamente, objetivamos analisar as relações entre a presença de função residual do CFTRe a concentração de cloro no suor, fenótipo pancreático, presença de Pseudomonas aeruginosa, função pulmonar e genótipo na amostra de pacientes comFC. Foi realizado um estudo transversal com realização da DPN em um grupo de pacientes com FC (n=29, idade:15±6 anos) e dois grupos controle: não=FC (n=19, idade: 15 ± 10 anos) e sadios (n=19, idade: 17 ± 8 anos). Os resultados demonstraram que os valores da DPN são significativamente diferentes no grupo FC (FC: DPNmax: -34 ± 9mV, Δamil: -20 ± 9mV, ΔCl: 4 ± 5mV, Δamilo-iso: -19 ± 9 mV e indiceDPN: 0.85 ± 0.23; não-FC:DPNmax: -14 ± 5mV, Δamil: -6 ± 3mV, ΔCl: 17 ± 9mV, Δamilo-iso: -1 ± 4 mV e indiceDPN: 0.11 ± 0.11) e sadios: DPNmax: -15 ± 4mV, Δamil: -6 ± 3mV, ΔCl: 11 ± 7mV, Δamilo-iso: -2 ± 4 mV e indiceDPN: 0.20±0.14),com sensibilidade e especificidade de 95-96% e concordância de resultado entre as duas narinas maior para a DPNmax (r=0,934). A função residual da CFTR não mostrou relação com nenhum dos parâmetros fenotípicos avaliados. Somente mostrou relação com a gravidade do genótipo. Entretanto, foi observada relação entre os parâmetros que avaliam a hiperfunção do ENaC existente na FC e o fenótipo. Concluímos com este trabalho que foi possível reproduzir e padronizar esta técnica da DPN e demonstrar que o fenótipo da FC está mais relacionado à alteração do transporte do íon sódio através do ENaC do que à presença de função residual da CFTR.<br>Nasal potential difference test (NPD) is a test that measures the bioelectrical difference across the nasal epithelium, which results from transepithelial ion transport of sodium (Na+), by ENaC channels (Epitelial Na+ Channel) and chloride (Cl-), by CFTR (Cystic Fibrosis Transmembrane Conductance Regulator).NPD has been used as a diagnostic tool in CFTR related disorders, such as Cystic Fibrosis (CF). CF is an autosomal recessive genetic disease caused by mutations that affect the function of the CFTR channel (andsecondarily of the EnaC)and lead to manifestations in various organs. Normally sweat chloride concentration > 60 mEq / L and identification of two CFTR mutations confirm the CF diagnosis. However there are atypical cases with inconclusive sweat chloride or genetic where the electrophysiological characteristics induced by CFTR dysfunction has to be demonstrated for diagnosis. The correct identification of these cases is important for institution of appropriate treatment and definition of prognosis. The objective of this study was to standardize the NPD for its future application as a diagnostic tool through the determination of reference values, sensibility and specificity and agreement of the results between both examined nostrils. Secondarily, we analyzed the relations between residual CFTR function and sweat chloride concentration, pancreatic phenotype, Pseudomonas aeruginosa positivity, pulmonary function and genotype in the sample of CF patients. It was a transversal study where the NPD was measured in a group of CF patients (n = 29, age: 15 ± 6 years) and two control groups: non-CF (n = 19, age: 15 ± 10 years) and healthy (n = 19, age: 17 ± 8 years). The results showed that NPD was significantly different in CF (NPDmax: -34 ± 9mV, Δamil: -20 ± 9mV, ΔCl: 4 ± 5mV, Δamilo-iso: -19 ± 9 mV e NPDindex: 0.85 ± 0.23; non-CF: NPDmax: -14 ± 5mV, Δamil: -6 ± 3mV, ΔCl: 17 ± 9mV, Δamilo-iso: -1 ± 4 mV and NPDindex: 0.11 ± 0.11) and healthy: NPDmax: -15 ± 4mV, Δamil: -6 ± 3mV, ΔCl: 11 ± 7mV, Δamilo-iso: -2 ± 4 mV and NPDindex: 0.20±0.14) with sensibility and specificity of 95-96% and agreement between both nostrils greater for NPDmax (r=0.934). The residual CFTR function did not show relation with all phenotypic parameters evaluated. It just showed relation with genotype severity. Indeed it was observed a relation between the parameters that assess the ENaC hyperfunction that occurs in CF and the phenotype. We concluded with this study that was possible to reproduce and to standardize the NPD and to demonstrate that the phenotype is more related to sodium transport alterations through ENaC than to the presence of residual CFTR function.
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Wilfong, Erin R. "The role of nerve growth factor in neuropeptide up-regulation in trigeminal ganglia neurons following irritant exposure." Morgantown, W. Va. : [West Virginia University Libraries], 2003. http://etd.wvu.edu/templates/showETD.cfm?recnum=3109.
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Thesis (Ph. D.)--West Virginia University, 2003.<br>Title from document title page. Document formatted into pages; contains xiii, 82, [148] p. : ill. (some col.). Includes abstract. Includes bibliographical references.